Patients with multiple sclerosis, spinal cord trauma, amyotrophic lateral sclerosis and other neurologic illnesses are often disabled by flexor spasms, hyperreflexia and increased tone. The neuronal mechanisms underlying these abnormalities are poorly understood, however the removal of spinal cord inhibitory interneurons from supraspinal control may explain these symptoms of spasticity. There are several types of inhibitory interneurons which can be distinguished pharmacologically and biochemically. Gamma-aminobutyric acid (GABA) is the putative transmitter for interneurons mediating presynaptic inhibition. Glycine is the presumed transmitter for cells mediating reciprocal Ia and recurrent inhibition. Physiologic studies indicate an underactivity of all these interneurons in spasticity as well as dysfunction of descending biogenic amine pathways. Studies have not evaluated the functional significance of these changes or related them to specific symptoms. The proposed experiments will measure a) the endogenous levels of GABA, glycine, norepinephrine and serotonin, b) the inactivation of these transmitters by high affinity reuptake systems, and c) the synaptic receptors for these transmitters during the development of spasticity after spinal cord transection. These biochemical variables will be correlated with the clinical development of spasticity. The same parameters will then be measured after selective lesions of the cortico-spinal, rubrospinal and vestibulospinal tracts to ascertain if specific lesions differentially effect these neurotransmitter systems. These studies will provide a scientific basic for more appropriate treatment of selected symptoms of spasticity.